CA2184824A1 - Peptides antagonistes de type bradykinine, incorporant des derives de substitution en n de glycines - Google Patents
Peptides antagonistes de type bradykinine, incorporant des derives de substitution en n de glycinesInfo
- Publication number
- CA2184824A1 CA2184824A1 CA002184824A CA2184824A CA2184824A1 CA 2184824 A1 CA2184824 A1 CA 2184824A1 CA 002184824 A CA002184824 A CA 002184824A CA 2184824 A CA2184824 A CA 2184824A CA 2184824 A1 CA2184824 A1 CA 2184824A1
- Authority
- CA
- Canada
- Prior art keywords
- arg
- gly
- pro
- thi
- ser
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 77
- 108010049175 N-substituted Glycines Proteins 0.000 title claims abstract description 34
- 239000003152 bradykinin antagonist Substances 0.000 title claims abstract description 32
- UYRCOTSOPWOSJK-JXTBTVDRSA-N bradykinin antagonist Chemical compound C1C2=CC=CC=C2CC1[C@@H](NC(=O)C(CO)NC(=O)C(NC(=O)CNC(=O)[C@H]1N(C[C@H](O)C1)C(=O)C1N(CCC1)C(=O)C(CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=N)CCCCCCC(=N)N[C@H](CCCNC(N)=N)C(=O)NC(CCCNC(N)=N)C(=O)N1C(CCC1)C(=O)N1[C@@H](C[C@@H](O)C1)C(=O)NCC(=O)NC(C1CC2=CC=CC=C2C1)C(=O)NC(CO)C(=O)N[C@H](C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(N)=N)C(O)=O)C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(=N)N)C(O)=O UYRCOTSOPWOSJK-JXTBTVDRSA-N 0.000 title claims abstract description 22
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 19
- 101800004538 Bradykinin Proteins 0.000 claims abstract description 52
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims abstract description 52
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims abstract description 48
- 208000002193 Pain Diseases 0.000 claims abstract description 9
- 206010061218 Inflammation Diseases 0.000 claims abstract description 3
- 230000004054 inflammatory process Effects 0.000 claims abstract description 3
- 229940024606 amino acid Drugs 0.000 claims description 69
- 235000001014 amino acid Nutrition 0.000 claims description 65
- -1 aromatic amino acid Chemical class 0.000 claims description 58
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 150000001413 amino acids Chemical class 0.000 claims description 43
- 239000005557 antagonist Substances 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 239000004475 Arginine Substances 0.000 claims description 20
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 19
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 150000001875 compounds Chemical class 0.000 claims description 16
- 239000004471 Glycine Substances 0.000 claims description 14
- 125000003630 glycyl group Chemical class [H]N([H])C([H])([H])C(*)=O 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 9
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 9
- 239000004472 Lysine Substances 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical group OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 7
- 125000000539 amino acid group Chemical group 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 6
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 6
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 6
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229960003104 ornithine Drugs 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- XBPKRVHTESHFAA-ZCFIWIBFSA-N (2r)-2-azaniumyl-2-cyclopentylacetate Chemical group OC(=O)[C@H](N)C1CCCC1 XBPKRVHTESHFAA-ZCFIWIBFSA-N 0.000 claims description 5
- LRHRHAWNXCGABU-UHFFFAOYSA-N 2-(cyclopentylazaniumyl)acetate Chemical group OC(=O)CNC1CCCC1 LRHRHAWNXCGABU-UHFFFAOYSA-N 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N benzocyclopentane Natural products C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 5
- FXHCFPUEIDRTMR-UHFFFAOYSA-N hydron;1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid;chloride Chemical group Cl.C1=CC=C2CNC(C(=O)O)CC2=C1 FXHCFPUEIDRTMR-UHFFFAOYSA-N 0.000 claims description 5
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 5
- WTOFYLAWDLQMBZ-UHFFFAOYSA-N 2-azaniumyl-3-thiophen-2-ylpropanoate Chemical compound OC(=O)C(N)CC1=CC=CS1 WTOFYLAWDLQMBZ-UHFFFAOYSA-N 0.000 claims description 4
- 229930182820 D-proline Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical group OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 claims description 3
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical group OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 claims description 3
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical group OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 3
- NPKSPKHJBVJUKB-UHFFFAOYSA-N N-phenylglycine Chemical compound OC(=O)CNC1=CC=CC=C1 NPKSPKHJBVJUKB-UHFFFAOYSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Substances 0.000 claims description 3
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 230000001575 pathological effect Effects 0.000 claims description 3
- 150000003053 piperidines Chemical class 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- WAMWSIDTKSNDCU-SSDOTTSWSA-N (2r)-2-azaniumyl-2-cyclohexylacetate Chemical group OC(=O)[C@H](N)C1CCCCC1 WAMWSIDTKSNDCU-SSDOTTSWSA-N 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- UHNMIDKSDRGICN-UHFFFAOYSA-N 2-(2-phenylethylazaniumyl)acetate Chemical compound OC(=O)CNCCC1=CC=CC=C1 UHNMIDKSDRGICN-UHFFFAOYSA-N 0.000 claims description 2
- 229930182832 D-phenylalanine Chemical group 0.000 claims description 2
- 125000000180 D-prolyl group Chemical group N1[C@@H](C(=O)*)CCC1 0.000 claims description 2
- JLXVRFDTDUGQEE-YFKPBYRVSA-N Gly-Arg Chemical compound NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N JLXVRFDTDUGQEE-YFKPBYRVSA-N 0.000 claims description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 2
- PSFABYLDRXJYID-VKHMYHEASA-N N-Methylserine Chemical compound CN[C@@H](CO)C(O)=O PSFABYLDRXJYID-VKHMYHEASA-N 0.000 claims description 2
- 108010077895 Sarcosine Proteins 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 235000004279 alanine Nutrition 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- IJVMOGKBEVRBPP-ZETCQYMHSA-N dcpg Chemical compound OC(=O)[C@@H](N)C1=CC=C(C(O)=O)C(C(O)=O)=C1 IJVMOGKBEVRBPP-ZETCQYMHSA-N 0.000 claims description 2
- 229940043230 sarcosine Drugs 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 125000005000 thioaryl group Chemical group 0.000 claims description 2
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims description 2
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 102100035792 Kininogen-1 Human genes 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 229960002429 proline Drugs 0.000 claims 3
- 229960001153 serine Drugs 0.000 claims 3
- 125000004103 aminoalkyl group Chemical group 0.000 claims 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- 229960002591 hydroxyproline Drugs 0.000 claims 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical group OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 claims 1
- CCAIIPMIAFGKSI-DMTCNVIQSA-N (2s,3r)-3-hydroxy-2-(methylazaniumyl)butanoate Chemical compound CN[C@@H]([C@@H](C)O)C(O)=O CCAIIPMIAFGKSI-DMTCNVIQSA-N 0.000 claims 1
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- OQMYZVWIXPPDDE-UHFFFAOYSA-N 2-(cyclohexylazaniumyl)acetate Chemical compound OC(=O)CNC1CCCCC1 OQMYZVWIXPPDDE-UHFFFAOYSA-N 0.000 claims 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- SCIFESDRCALIIM-UHFFFAOYSA-N N-Me-Phenylalanine Natural products CNC(C(O)=O)CC1=CC=CC=C1 SCIFESDRCALIIM-UHFFFAOYSA-N 0.000 claims 1
- PSFABYLDRXJYID-UHFFFAOYSA-N N-methyl-DL-serine Natural products CNC(CO)C(O)=O PSFABYLDRXJYID-UHFFFAOYSA-N 0.000 claims 1
- SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 claims 1
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- 230000004706 cardiovascular dysfunction Effects 0.000 claims 1
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- 102400000967 Bradykinin Human genes 0.000 abstract description 44
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- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003148 prolines Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 1
- 230000036964 tight binding Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/18—Kallidins; Bradykinins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Genetics & Genomics (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
L'invention concerne des peptides du type bradykinine contenant des glycines substituées en N, et plus particulièrement des peptides antagonistes de la bradykinine utiles pour le traitement de pathologies induites par la bradykinine, dont la douleur et l'inflammation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20811594A | 1994-03-09 | 1994-03-09 | |
| US08/208,115 | 1994-03-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2184824A1 true CA2184824A1 (fr) | 1995-09-14 |
Family
ID=22773240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002184824A Abandoned CA2184824A1 (fr) | 1994-03-09 | 1995-03-07 | Peptides antagonistes de type bradykinine, incorporant des derives de substitution en n de glycines |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US5700779A (fr) |
| EP (1) | EP0813544B1 (fr) |
| JP (1) | JPH09511500A (fr) |
| KR (1) | KR100360639B1 (fr) |
| CN (1) | CN1150206C (fr) |
| AT (1) | ATE280777T1 (fr) |
| AU (1) | AU696429B2 (fr) |
| CA (1) | CA2184824A1 (fr) |
| DE (1) | DE69533704D1 (fr) |
| TW (1) | TW408133B (fr) |
| WO (1) | WO1995024422A1 (fr) |
| ZA (1) | ZA951974B (fr) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648336A (en) * | 1994-11-18 | 1997-07-15 | University Of Colorado | Bradykinin antagonist peptides containing indane-substituted amino acids |
| EP0832106A2 (fr) * | 1995-06-05 | 1998-04-01 | Cortech, Inc. | Composes ayant une activite antagoniste de la bradykinine et une activite agoniste mu-opio de |
| US5849863A (en) * | 1995-09-08 | 1998-12-15 | University Of Colorado | Cytolytic bradykinin antagonists |
| DE19612067A1 (de) * | 1996-03-27 | 1997-10-02 | Hoechst Ag | Verwendung von Bradykinin-Antagonisten zur Herstellung von Arzneimitteln zur Behandlung von chronisch fibrogenetischen Lebererkrankungen und akuten Lebererkrankungen |
| FR2756566B1 (fr) | 1996-12-04 | 1999-01-08 | Fournier Ind & Sante | Peptides agonistes du recepteur b2 de la bradykinine, procede de preparation et utilisation en therapeutique |
| AU3511500A (en) | 1999-03-05 | 2000-09-21 | Trustees Of University Technology Corporation, The | Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide-induced clinical conditions |
| US6849605B1 (en) | 1999-03-05 | 2005-02-01 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of viral infections |
| WO2000051625A1 (fr) * | 1999-03-05 | 2000-09-08 | The Trustees Of University Technology Corporation | Inhibiteurs d'activite de serine protease, methodes et compositions de traitement de virus de l'herpes |
| AU3731400A (en) * | 1999-03-05 | 2000-09-21 | Trustees Of University Technology Corporation, The | Methods and compositions useful in inhibiting apoptosis |
| US7105172B1 (en) | 1999-11-18 | 2006-09-12 | Bolla John D | Treatment of rosacea |
| US6699486B1 (en) | 1999-11-18 | 2004-03-02 | Bolla Corporation | Treatment or prevention of photoaging and skin cancer |
| CA2423876C (fr) * | 2003-04-01 | 2013-05-28 | Universite De Sherbrooke | Nouveaux antagonistes selectifs du recepteur peptidique de la bradykinine (bk) b1 et leurs utilisations |
| US20040220242A1 (en) * | 2003-05-02 | 2004-11-04 | Leland Shapiro | Inhibitors of serine protease activity, methods and compositions for treatment of nitric oxide induced clinical conditions |
| US7605120B2 (en) * | 2003-10-22 | 2009-10-20 | Amgen Inc. | Antagonists of the brandykinin B1 receptor |
| US7932228B2 (en) * | 2004-08-19 | 2011-04-26 | Societe de Commercialisation des Produits de la Recherche Applique Socpra Sciences Sante et Humaines S.E.C. | Method of treating bone or prostate cancer with selective bradykinin B1 receptor antagonists |
| US20080095849A1 (en) * | 2005-04-25 | 2008-04-24 | Amgen Inc. | Peptide sustained release compositions and uses thereof |
| US7403325B2 (en) * | 2006-05-19 | 2008-07-22 | Xerox Corporation | Electrophoretic display device |
| US8476408B2 (en) * | 2008-06-13 | 2013-07-02 | Alize Pharma Sas | Unacylated ghrelin and analogs as therapeutic agents for vascular remodeling in diabetic patients and treatment of cardiovascular disease |
| FR2974182B1 (fr) * | 2011-04-14 | 2013-04-26 | Univ Grenoble 1 | Diagnostic et traitement de l'angioedeme |
| CN102295711A (zh) * | 2011-08-23 | 2011-12-28 | 湖北宝迪农业科技有限公司 | 从猪肺中提取肝素钠并联产多肽蛋白粉的工艺 |
| WO2013043669A1 (fr) * | 2011-09-21 | 2013-03-28 | The Board Of Regents Of The University Of Texas System | Compositions peptoïdes pour le traitement de la maladie d'alzheimer et d'un trouble de l'expansion de polyglutamine |
| CA3001065A1 (fr) | 2015-10-14 | 2017-04-20 | Xiaoxi WEI | Compositions et procedes permettant de reduire la formation de cristaux de glace |
| CN116554267A (zh) * | 2022-01-30 | 2023-08-08 | 江苏众红生物工程创药研究院有限公司 | 聚乙二醇修饰的激肽或其变体和药物应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2964956D1 (en) * | 1978-07-18 | 1983-04-07 | Kabi Ab | Bradykinin inhibiting tripeptide derivatives, process for their preparation and pharmaceutical preparations containing them |
| US4693993A (en) * | 1985-06-13 | 1987-09-15 | Stewart John M | Bradykinin antagonist peptides |
| DE4013270A1 (de) * | 1990-04-26 | 1991-10-31 | Hoechst Ag | Peptide mit bradykinin-antagonistischer wirkung |
| IE63490B1 (en) * | 1988-11-24 | 1995-05-03 | Hoechst Ag | Peptides having bradykinin antagonist action |
| DE69226708T2 (de) * | 1991-04-19 | 1999-04-15 | Scios Nova Inc., Mountain View, Calif. | Bradykinin typische peptide |
| EP0529499A1 (fr) * | 1991-08-22 | 1993-03-03 | Hoechst Aktiengesellschaft | Compositions à utilisation topique pour l'application au nez ou aux yeux à base d'antagonistes de bradykinine |
| WO1993011789A1 (fr) * | 1991-12-12 | 1993-06-24 | Scios Nova Inc. | Modifies en position (7) de peptides antagonistes de la bradykinine |
| TW258739B (fr) * | 1992-04-04 | 1995-10-01 | Hoechst Ag | |
| JPH11500100A (ja) * | 1993-09-09 | 1999-01-06 | サイオス ノバ インコーポレイテッド | 偽ペプチドおよび非ペプチドブラジキニンレセプターアンタゴニスト |
-
1995
- 1995-03-07 KR KR1019960704967A patent/KR100360639B1/ko not_active Expired - Fee Related
- 1995-03-07 CA CA002184824A patent/CA2184824A1/fr not_active Abandoned
- 1995-03-07 WO PCT/US1995/002399 patent/WO1995024422A1/fr not_active Ceased
- 1995-03-07 AT AT95911948T patent/ATE280777T1/de not_active IP Right Cessation
- 1995-03-07 AU AU19325/95A patent/AU696429B2/en not_active Ceased
- 1995-03-07 DE DE69533704T patent/DE69533704D1/de not_active Expired - Lifetime
- 1995-03-07 JP JP7523493A patent/JPH09511500A/ja not_active Ceased
- 1995-03-07 CN CNB951930176A patent/CN1150206C/zh not_active Expired - Fee Related
- 1995-03-07 EP EP95911948A patent/EP0813544B1/fr not_active Expired - Lifetime
- 1995-03-09 ZA ZA951974A patent/ZA951974B/xx unknown
- 1995-03-15 TW TW084102476A patent/TW408133B/zh not_active IP Right Cessation
-
1996
- 1996-06-20 US US08/668,100 patent/US5700779A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE280777T1 (de) | 2004-11-15 |
| ZA951974B (en) | 1995-12-11 |
| EP0813544A1 (fr) | 1997-12-29 |
| AU1932595A (en) | 1995-09-25 |
| KR100360639B1 (ko) | 2003-01-30 |
| AU696429B2 (en) | 1998-09-10 |
| US5700779A (en) | 1997-12-23 |
| EP0813544A4 (fr) | 1998-01-07 |
| TW408133B (en) | 2000-10-11 |
| DE69533704D1 (de) | 2004-12-02 |
| CN1150206C (zh) | 2004-05-19 |
| CN1148393A (zh) | 1997-04-23 |
| EP0813544B1 (fr) | 2004-10-27 |
| WO1995024422A1 (fr) | 1995-09-14 |
| JPH09511500A (ja) | 1997-11-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |